Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.
I am not sure it is clear from the abstract, but the trick is to focus on the pro-longevity effects of nearly 4000 mutants of a single E. coli strain by establishing small colonies of the animals, each hosting a single mutant strain as its microbiome. A sub-set of these mutants upregulated the production of colanic acid. Since colanic acid had previously been studied as an agent in bacterial quorum sensing, one comes away from the paper with the somewhat eerie sensation that gut microbiota are conversing with their cousins inside nearly all eukaryotic cells, mitochondria.
This paper is reviewed in some depth in the following podcast:
http://www.microbe.tv/twim/twim-176/